The Program Project (Pennsylvania Muscle Institute) functions as a multi-institutional, interdisciplinary program for collaborative studies on normal and diseased vascular smooth, cardiac and skeletal muscle and platelet function. Major areas investigated are: the structure and the biochemical and mechanical kinetics of myosin crossbridges, excitation-contraction coupling, stimulation-secretion coupling and shape change in blood platelets, the interaction of actin with actin-binding proteins and the developmental differentiation of sarcomeres and other organized components of contractile cells. The development of the following novel methods and instrumention, for this research, is a specific goal of the Program: biological electron probe and electron energy loss analysis, the synthesis of inert photolabile precursors caged compounds) of biologically active molecules for kinetic studies through activation with laser flash photolysis; scanning confocal and fluorescent light microscopy, microinjection of antibodies, mRNA and antisense messengers for developmental studies, and the development and use of antibodies directed to contractile, structural and regulatory proteins as probes of cell differentiation and contractile function. The longterm scientific aims and technologies developed in the Program Project are directed to understanding the pathophysiology of diseases of the heart and vascular smooth muscle.